A Phase II Study of Pazopanib in Asian Patients with Recurrent/Metastatic Nasopharyngeal Carcinoma

• Published in: Clinical cancer research 2011-08, Vol.17 (16), p.5481-5489
• Main Authors: LIM, Wan-Teck, NG, Quan-Sing, TONG SAN KOH, TOH, Chee-Keong, TAN, Eng-Huat, IVY, Percy, LEONG, Swan-Swan, SINGH, Onkar, CHOWBAY, Balram, FEI GAO, CHOON HUA THNG, GOH, Boon-Cher, SHAO-WENG TAN, Daniel
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - therapeutic use; Anorexia - chemically induced; Antineoplastic agents; Asian Continental Ancestry Group; Biological and medical sciences; Carcinoma; Diarrhea - chemically induced; Drug Administration Schedule; Fatigue - chemically induced; Female; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - drug therapy; Nasopharyngeal Neoplasms - ethnology; Nasopharyngeal Neoplasms - pathology; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neovascularization, Pathologic - ethnology; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - prevention & control; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Pyrimidines - adverse effects; Pyrimidines - pharmacokinetics; Pyrimidines - therapeutic use; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Sulfonamides - therapeutic use; Treatment Outcome; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Vomiting - chemically induced
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-10-3409

Nasopharyngeal carcinoma is endemic in Asia and angiogenesis is important for growth and progression. We hypothesized that pazopanib would have antiangiogenic activity in nasopharyngeal carcinoma. A single arm monotherapy study of pazopanib in patients with WHO type II/III nasopharyngeal carcinoma who had metastatic/recurrent disease and failed at least one line of chemotherapy. A Simon's optimal 2-stage design was used. Patients with Eastern Cooperative Oncology Group (ECOG) 0-2 and adequate organ function were treated with pazopanib 800 mg daily on a 21-day cycle. The primary endpoint was clinical benefit rate (CR/PR/SD) achieved after 12 weeks of treatment. Secondary endpoints included toxicity and progression-free survival. Exploratory studies of dynamic-contrast enhanced computed tomography (DCE-CT) paired with pharmacokinetics (PK) of pazopanib was done. Thirty-three patients were accrued. Patients were ECOG 0-1 with median age of 50 years (range 36-68). There were 2 (6.1%) partial responses, 16 (48.5%) stable disease, 11 (33.3%) progressive disease, 4 (12.1%) were not evaluable for response. The clinical benefit rate was 54.5% (95% CI: 38.0-70.2). Ten patients (30.3%) received more than 6 cycles (4 months) of treatment and 7 (21.2%) had PR/SD that lasted at least 6 months. One patient each died from epistaxis and myocardial infarction. Common grade 3/4 toxicities included fatigue (15.2%), hand-foot syndrome (15.2%), anorexia (9.1%), diarrhea (6.1%), and vomiting (6.1%). Serial DCE-CT scans show significant reductions in tumor blood flow, permeability surface area product, and fractional intravascular blood volume. Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile.